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Abstract
Objective To assess cross-sectional associations of neurofibrillary tangles, measured by tau-PET, with cognitive performance in cognitively unimpaired (CU) adults.
Methods Tau- and amyloid-PET were performed in 579 CU participants aged 50–98 from the population-based Mayo Clinic Study of Aging. Associations between tau-PET signal in 43 brain regions and cognitive test scores were assessed using penalized linear regression. In additional models, participants were classified by normal/abnormal global amyloid-PET (A+/A−) and normal/abnormal regional tau-PET (T+/T−). Regional tau-PET cutpoints were defined as standardized uptake value ratio (SUVR) greater than the 95th percentile of tau-PET SUVR in that region among 117 CU participants aged 30–49.
Results Higher tau-PET signal was associated with poorer memory performance in all medial temporal lobe (MTL) regions and also in the middle temporal pole and frontal olfactory regions. The largest association with tau-PET and memory z scores was seen in the entorhinal cortex; this association was independent of tau-PET signal in other brain regions. Tau-PET in the entorhinal cortex was also associated with poorer global and language performance. In the entorhinal cortex, T+ was associated with lower memory performance among both A− and A+.
Conclusions Tau deposition in MTL regions, as reflected by tau-PET signal, was associated with poorer performance on memory tests in CU participants. The association with entorhinal cortex tau-PET was independent of tau-PET signal in other brain regions. Longitudinal studies are needed to understand the fate of CU participants with elevated medial temporal tau-PET signal.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- CU=
- cognitively unimpaired;
- MCALT=
- Mayo Clinic Adult Lifespan Template;
- MCSA=
- Mayo Clinic Study of Aging;
- MTL=
- medial temporal lobe;
- NFT=
- neurofibrillary tangle;
- PART=
- primary age-related tauopathy;
- PVC=
- partial volume correction;
- ROI=
- region of interest;
- SUVR=
- standardized uptake value ratio
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received July 24, 2018.
- Accepted in final form February 19, 2019.
- © 2019 American Academy of Neurology
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